megalin/cubilin介导的内吞作用参与牙釉质发育机制的研究

釉质中蛋白质过量残留会导致釉质晶体结构缺陷和矿化不全，成釉细胞对蛋白质的再吸收是釉质发育的重要环节，这一过程的机制并不清楚。近期研究发现成釉细胞可通过内吞途径来清除釉质基质蛋白，而megalin和cubilin是两个重要内吞介导因子，我们的前期研究发现了megalin/cubilin在成熟期成釉细胞中的表达，因此我们提出假设：成釉细胞通过megalin/cubilin介导的内吞作用再吸收白蛋白、釉质基质蛋白及其降解产物。为验证此假设，我们拟观察megalin/cubilin在牙发育全程的表达模式以及内吞囊泡的形成，采用细胞学实验观察megalin/cubilin对成釉细胞系的蛋白摄取能力的影响，对megalin和cubilin在成釉细胞介导内吞作用的信号途径进行初步的探索，为探讨釉质发育不全的病因提供新的途径。

The resorption of protein by ameloblasts is an important process of enamel development. The enamel with excessive protein residue will lead to the defect of crystal structure and hypomineralization of enamel. However, the mechanism of protein clearance and resorption during enamel maturation is not clear. Recent studies have found that ameloblasts can remove enamel matrix proteins through active endocytosis, but the removal of albumin in enamel has not been reported. Our previous study found the expression of Megalin/Cubilin in ameloblasts, and it was reported that Megalin and Cubilin were involved in the reabsorption of albumin through endocytosis in renal tubular epithelium. Since Megalin/Cubilin is an endocytic mediator of multiple ligands, we hypothesized that ameloblasts re-absorb albumin, enamel matrix proteins and their degradation products through Megalin/Cubilin mediated endocytosis. To test this hypothesis, we will observe the expression pattern of Megalin/Cubilin and the formation of endocytic vesicles in all stages of tooth development. The protein uptake ability of ameloblast cell line and the function of Megalin/Cubilin function in this process will be observed by cytological experiments. The potential mechanism of the signaling pathway mediated by megalin/cubilin will be discussed. This study aims to explore a new approach for the pathogenesis of Amelogenesis imperfecta.